Prognostic significance of micro RNA 150 marker in BCR-ABL positive chronic myeloid leukaemia patients on imatinib mesylate

Abstract

Background: Micro-RNAs control gene expression by destabilizing targeted transcripts and inhibiting their translation. In chronic myeloid leukaemia (CML), abnormal expressions of miRNAs have been described. The current treatment for newly diagnosed cases of CML is imatinib mesylate which produces rapid haematological responses. It is currently impossible to predict whether a patient will develop resistance to imatinib mesylate. This makes identification of predictors of resistance to imatinib an important goal in management of patients with CML. MicroRNA expression patterns can be used to predict outcome which can be remission or relapse. This study therefore, was set to assess the possible use of microRNA 150 for prognostication.Methods: Fifty peripheral blood samples previously collected from CML patients who were being treated with imatinib mesylate and stored in the refrigerator at +4°C were analyzed for the expression of microRNAs 150. Total RNA was extracted from guanidium isothiocynate (GITC) lysate of the blood samples using RNeasy mini spin column. The total RNA was converted to complimentary DNA by random hexamer priming using Murine Moloney Leukaemia Virus Reverse Transcriptase. Real time Multiplex PCR was used for detecting Breakpoint Cluster Region-Abelson Murine Leukaemia (BCR-ABL) transcript type.Results: The patients’ samples showed an expression of miRNA-150. Correlation of BCR-ABL ratio with miRNA-150 was done and the Spearman correlation coefficient (Rho) between BCR-ABL1 and miRNA-150 was 0.442 (p = 0.001; CI = 0.18-0.65) showing that there was a positive correlation between BCR-ABL1 and miRNA-150. The coefficient of determination was 20% (CI = 3-42%), which implies that about 20% of BCR-ABL1 ratio could be accounted for by the miRNA-150 values.Conclusions: Therefore, once patients who are on imatinib achieve molecular remission of the CML, the miRNA-150 can be useful in predicting outcome which could be relapse or complete molecular remission but is weak at diagnosis in predicting such outcome.

role of miRNA -150 between different BCR-ABL p210 transcript levels and between different levels of imatinib optimal response in CML patients

“…Prior to the introduction of imatinib, older age was a risk factor. Since then, CML patients' outcomes have improved, and older age appears to have lost its negative impact [21]. white blood cells count they showed no significant difference between both patients group, also between patients different response groups and control group, our studied failure response CML patients were with failure molecular response.…”

“…At the molecular level, BCR-ABL and miRNA-150 had a positive connection. This means that once patients on imatinib have achieved molecular remission from chronic myeloid leukemia, miRNA-150 can be used to predict remission outcome [21]. TKI inhibit BCR-ABL oncoprotein phosphorylation by blocking the ATPbinding site of the kinase domain of ABL, the activity of this compound results in the transcriptional modulation of various genes involved in the control of the cell cycle, cell adhesion, and cytoskeleton organization, leading the Ph-positive cell to an apoptotic death.…”